OVERALL ? PROJECT SUMMARY/ ABSTRACT The Johns Hopkins Alzheimer's Disease Research Center (JHADRC) is an integrated program of investigators whose overarching goal is to improve understanding of the earliest phases of AD and to expand therapeutic approaches. The overall scientific focus of the JHADRC is on the earliest stages of AD and related disorders in humans and in model systems, through characterizing the earliest clinical and pathophysiological processes, and by identifying cellular and molecular events that contribute to the abnormalities in model systems that capture aspects of the human disorders. We also focus efforts on improving care of patients in the symptomatic phases of disease. We have made substantial progress with these research goals during the current funding cycle, supported by a P50 center grant, and propose to continue and expand this work in the next funding cycle, through a P30 grant mechanism. The proposed Center consists of 6 Cores and one component : (1) the Administrative Core (Core A), (2) the Clinical Core (Core B), (3) the Data Management and Biostatistics Core (Core C), (4) the Neuropathology Core (Core D), (5) the Outreach, Recruitment and Engagement Core (Core E), (6) the Biomarker Core (Core F) and (7) the Research Education Component (REC). In this application we are also including funds for 3 Developmental Projects; we anticipate funding one developmental project for 2 years and two developmental projects for 3 years each.